Method for processing aqueous fermentation broths

ABSTRACT

A method for processing aqueous fermentation broths in a bioreactor vessel, in which a foam inhibitor is added to the fermentation broth in the bioreactor vessel in order to prevent the accumulation and buildup of foam in the bioreactor vessel caused by oxygen sparging of the fermentation broth contained therein. The aqueous fermentation broth processed in the bioreactor vessel is conveyed as a feed solution to an ultrafiltration system including a membrane for concentrating the aqueous fermentation broth. The ultrafiltration system is typically located downstream of the bioreactor vessel. The improvement involves reducing the amount of fouling of the membrane in the ultrafiltration system by adding to the aqueous fermentation broth in the bioreactor vessel as the foam inhibitor, an antifoam which is an oil based liquid in the form of droplets, the droplets of the oil based liquid antifoam being dispersed, encased, entrapped, and imbedded, within solid particles of a water soluble encapsulating material.

BACKGROUND OF THE INVENTION

This invention relates to an improved process for treating fermentationbroths in which a solid particulate form of encapsulated antifoam isemployed in a bioreactor vessel in order that fouling be reduced inultrafiltration equipment employed downstream of the bioreactor vesselduring concentration of the broth.

Fermentation processing involves organisms such as bacteria, yeast, andfungus, in a culture medium of a broth including starch, glucose,oxygen, and various proteins. The aqueous broth is allowed to fermentfor a number of days, and as the broth is fermenting, the broth issupplied with a constant amount of oxygen in order to increase the rateof aerobic conversion. As a result of such oxygen sparging, and becauseof the presence of surface active proteins, a substantial amount of foamis produced in the bioreactor vessel. It has therefore been conventionalpractice to add a foam inhibitor to the broth in order to reduce theaccumulation of foam. Traditionally, such foam inhibitors have been inthe form of emulsions including droplets of oil dispersed in water. Suchemulsion type antifoam formulations have necessarily includedsurfactants, coagulants, and gelatinous thickeners, for the purpose ofstabilizing these antifoam formulations.

Following completion of the microbial activity in the bioreactor, it isnecessary to process the fermentation broth by concentrating the brothin order to separate desired products from the impurities contained inthe broth. This processing is typically conducted by passing thefermentation broth from the bioreactor to a filtration unit locateddownstream of the bioreactor. The filtration systems employed areultrafiltration units employing membranes. In these separation units,there is generated a high pressure bulk flow of broth across hydrophobicmembranes having pore sizes ranging from 0.01 to 1.0 micron. The brothpasses through the membrane, while the impurities sought to be separatedare retarded by the membrane. These impurities constitute, for example,cells, proteins, and bacteria. It has been found that such membranes arehighly sensitive to fouling and clogging, with the result that thefiltration rate, expressed as flux through the membrane, is inhibited;the product yield is reduced; and there is a corresponding reduction inthe life-span of the membrane itself. One contributing factor tomembrane fouling, clogging, and filtration rate inhibition, is believedto be the presence in the antifoam emulsion of the various surfactants,coagulants, and thickeners, used to stabilize emulsion type antifoams.These surfactants, coagulants, and thickeners, form a gel layer at theinterface of the membrane and the aqueous phase, and the gel layerclings to the surface of the membrane, inhibiting the filtration rate ofthe effluent therethrough.

Thus, it should be apparent that there exists a need for an antifoamformula-ion which will effectively inhibit the formation of foam in thefermentation broth in the bioreactor, and which will also allow highefficiency filtration rates through the membrane, and without theformation of flux inhibiting gel layers prone to foul the membrane andreduce its efficiency.

Encapsulated antifoams are not new, nor is the encapsulation ofantifoams in water soluble materials new or novel. For example, it hasrecently been reported that a new process for encapsulating liquids orsolids in a cornstarch matrix for slow release has been developed by theUSDA Northern Regional Research Center. The matrix consists of acompound produced from amylose and amylopectin. In order to encapsulatea herbicide, for example, cornstarch is cooked in a jet of steam togelatinize the starch. The herbicide, insect lure, plant growthregulator, fertilizer, medicine, flavoring, coloring, or vitamin, ismixed in; dried; and the mixture may be crumbled or ground to granulesor particles, respectively. In United Kingdom Published UnexaminedApplication No. 2180254, filed Sept. 10, 1986, and published Mar. 25,1987, a sugar such as sucrose is used in a detergent composition butacts, rather than an encapsulant, to increase the dispersibility of thedetergent. In European Published Unexamined Application No. 0171457,filed Aug. 17, 1984, published Feb. 19, 1986, particles of sugar such aslactose are embedded in a semi-permeable membrane and then dissolved,releasing water soluble actives.

In U.S. Pat. No. 3,159,585, issued Dec. 1, 1964, various oils such asvegetable fats are encapsulated with dextrins. Sugar in the form ofmixtures of mannitol, sorbitol, and refined cane sugar, are used toencapsulate mineral oil in U.S. Pat. No. 3,779,942, issued Dec. 18,1973. Fragrance oils, spice oils, perfume oils, and fruit flavors, aretaught in U.S. Pat. No. 3,971,852, issued July 27, 1976, to beencapsulated in a mixture of dextrin and a sugar such as sucrose,fructose, and glucose. In U.S. Pat. No. 4,481,157, issued Nov. 6, 1984,a mixture of gelatin, sorbitol, water, and a coagulant, such as a liquidparaffin, is used to encapsulate vegetable oil. A bulk laxativecontaining methylcellulose particulates encapsulated in sucrose isdisclosed in U.S. Pat. No. 4,732,917, issued Mar. 22, 1988.

A silicone antifoam formulation is disclosed in United Kingdom PatentNo. 892,787, granted Mar. 28, 1962, and in which an organosiloxaneemulsion including fume silica, is spray dried along withmethylcellulose in order to form encapsulated antifoam particles. Otherencapsulating materials are disclosed to be starch, gelatin, albumen,gum acacia, locust bean gum, carrageena, polyvinyl alcohol, polyethyleneglycol, and guar gum.

However, all of the foregoing references require the presence of one ormore of a surfactant, coagulant. thickener, or additive, in order tostabilize the system. In addition, none relate specifically toenvironments including ultrafiltration equipment or membrane separators,nor do the references relate to fluid treatment systems such asfermentation processes requiring such ultrafiltration equipment ormembrane separators.

There is described in PCT International Publication No. WO 86/05411,published Sept. 25, 1986, an ultrafiltration system that employs asilicone alkylene oxide copolymer as a foam inhibitor for the fluidsprocessed therein. This antifoam material is allegedly does notpermanently foul the membrane, in comparison to conventional antifoamformulations containing additives such as emulsifying agents. It isnoted, however, that in the event the membrane does become fouled, thatthe fouling process can be reversed by cleaning the membrane usingconventional techniques such as flushing the membrane with cold water orwith a mild bleach solution. The silicone alkylene oxide copolymericantifoam material of the PCT International Publication is also disclosedto be operable in functioning as a foam inhibitor in the absence ofemulsifiers, solvents, and finely divided insoluble matter.

In accordance with the present invention, a novel alternative foaminhibitor is provided, which foam inhibitor is effective for use, forexample, in methods for processing aqueous fermentation broths in abioreactor vessel, in which the broth is conveyed downstream as a feedsolution to an ultrafiltration system including a membrane forconcentrating the aqueous fermentation broth. The foam inhibitor is inthe form of an oil based liquid in the form of droplets, the droplets ofthe oil based liquid antifoam being dispersed, encased, entrapped, andimbedded, within solid particles of a water soluble encapsulatingmaterial. The encapsulated particulate antifoam is free of additivesknown to inhibit the filtration rate through the membrane, such assurfactants, coagulants, and thickeners. When added to the fermentationbroth, the bland encapsulating material of the present invention,dissolves and releases the additive free active antifoam ingredient intothe aqueous phase in the bioreactor vessel.

Unlike the silicone alkylene oxide copolymer of the PCT InternationalPublication referred to previously, the antifoams of the presentinvention meet the requirements of and are permissible in most foods, asestablished under rulings of the United States Food and DrugAdministration. Further, the materials of the present invention are inan otherwise solid particulate form, rendering them capable of aprogrammed form of release of the antifoam encapsulated therein, incontrast to the bulk fluids of the PCT International Publication.

SUMMARY OF THE INVENTION

This invention relates to a method for processing aqueous solutions in atreating vessel, in which a foam inhibitor is added to the treatingvessel in order to prevent the accumulation and buildup of foam therein,and in which the aqueous solution processed in the treating vessel isconveyed as a feed solution to an ultrafiltration system including amembrane. The ultrafiltration system is typically located downstream ofthe treating vessel, but the system can also constitute part of therecirculation process in certain instances as well. The improvementinvolves employing as the foam inhibitor in the treating vessel, anantifoam which is an oil based liquid in the form of droplets. Thedroplets of the oil based liquid antifoam are dispersed, encased,entrapped, and imbedded, within solid particles of a water solubleencapsulating material.

The invention is also directed to a method for processing aqueousfermentation broths in a bioreactor vessel, in which a foam inhibitor isadded to the fermentation broth in the bioreactor vessel in order toprevent the accumulation and buildup of foam in the bioreactor vessel,caused by oxygen sparging of the fermentation broth contained therein.The aqueous fermentation broth processed in the bioreactor vessel isconveyed as a feed solution to an ultrafiltration system, including amembrane for concentrating the aqueous fermentation broth. Theultrafiltration system is typically located downstream of the bioreactorvessel. The improvement in this process involves reducing the amount offouling of the membrane in the ultrafiltration system by adding to theaqueous fermentation broth in the bioreactor vessel as the foaminhibitor, an antifoam which is an oil based liquid in the form ofdroplets. The droplets of the oil based liquid antifoam are dispersed,encased, entrapped, and imbedded, within solid particles of a watersoluble encapsulating material.

In some particular and preferred embodiments of the present invention,the oil based liquid antifoam is selected from the group consisting ofsilicone oils, vegetable oils, and mineral oils. The water solubleencapsulating material is selected from the group consisting of sugarsand hydrolysis products of starch, and can include such materials asmaltodextrin, glucose, maltose, sucrose, fructose, xylose, and lactose.The antifoam should be otherwise free of surfactants, thickeners, andcoagulants, or other additives which tend to clog the membrane.

These and other features, objects, and advantages, of the presentinvention will become more apparent when considered in light of thefollowing detailed description thereof.

DETAILED DESCRIPTION OF THE INVENTION

Ultrafiltration is a separation technique in which a liquid includingsmall dissolved molecules is forced through a porous membrane. Largedissolved molecules, colloids, and suspended solids which do not migratethrough the membrane pores are retained. The membranes are typicallyconstructed of polymeric materials such as cellulose acetates,polyamides, polysulfones, vinyl chloride-acrylonitrile copolymers, andpolyvinylidene fluoride. The membrane may be employed in the form of aflat sheet; a parallel leaf cartridge including several flat plates eachwith a membrane on both sides; a plate and frame assembly; a spirallywound cartridge of a pair of membrane sheets separated by a flexibleporous support; supported tubes; and pleated sheets. Suchultrafiltration equipment is adapted to a wide variety of processingapplications including, for example, protein recovery; the manufactureof cheese and yogurt; the concentration of oil and water emulsions;lanolin recovery; the concentration and purification of enzymes;antibiotic manufacture; alcohol fermentation., sewage treatment; andblood fractionation and purification. One distinct disadvantage ofultrafiltration is that retained materials which do not pass through thepores of the membrane tend to collect on the surface of the membrane,forming a gel layer which limits the filtration rate expressed as flux.In order to minimize the thickness of the gel layer, such systems aredesigned so that the flow of influent sweeps across the membranesurface. Material is recirculated in order to maintain a sufficientvelocity across the surface of the membrane.

Often ultrafiltration units are used in processes wherein theultrafiltration equipment is deployed at a location downstream of atreatment type vessel. These vessels frequently require the addition offoam inhibiting agents during the treatment process. While such foaminhibiting agents are effective in preventing the buildup of foam in thetreatment vessel; the surfactants, coagulants, and thickeners, used tostabilize such antifoam agents, are one of the major contributors in themaintenance of the gel layer.

In an effort to minimize the contribution of materials to the gel layerformed at the surface of the membrane, the antifoam formulation of thepresent invention excludes surfactants, coagulants, and thickeners, orother additives, typically found in foam inhibiting agents. Exemplary ofmaterials sought to be excluded from the compositions of the presentinvention are common surfactants such as glycerol monostearate,polyoxyethylene sorbitan tristearate, and polyoxyethylene monostearate;and thickeners such as xanthan gums, hydroxypropyl methylcellulose, andcarboxy methylcellulose. This exclusion of additive materials isaccomplished by encapsulating the antifoam active ingredient in a watersoluble material in the form of a solid particulate. In this solidparticulate encapsulated form, the antifoam active ingredient isotherwise preserved in a stabilized fashion, and can be stored forextended periods of time prior to being used. Upon addition of theparticles of encapsulated antifoam to an aqueous system, the watersoluble material is dissolved, releasing the antifoam active ingredientinto the aqueous phase in order to perform its foam inhibiting function.

The water soluble material used to encapsulate the antifoam activeingredient in accordance with the present invention, can be either ahydrolysis product of starch such as maltodextrin, or a sugar such asglucose, maltose, sucrose, fructose, xylose, and lactose. Maltodextrinis the preferred encapsulating material because of its blandcharacteristics. The antifoam active may contain a finely dividedparticulate filler, typically, silica, in addition to the fluidcomponent of the antifoam. The fluid component of the antifoam activeingredient may be one or more of, or mixtures of, oil based liquids suchas mineral oils and vegetable oils. Preferred vegetable oils are soybeanoil, peanut oil, corn oil, rapeseed oil, coconut oil, palm oil, oliveoil, sesame oil, cottonseed oil, sunflower oil, and safflower oil. Theremay also be used, in addition to mineral oils and vegetable oils, an oilbased liquid of a silicone.

The term silicone denotes a polymer of the formula ##STR1## wherein n isan integer between zero and three, and m is two or more. The simplestsilicone materials are the polydimethylsiloxanes. Polydimethylsiloxaneshave the structure ##STR2## where x is an integer of from one to aboutone hundred thousand. The repeating unit of the polymer ##STR3## is thedimethylsiloxane unit. The terminal unit (Me3SiO) is the trimethylsiloxygroup. At low molecular weights, silicones are fluids, and at highmolecular weights, they are gums which may be cross-linked to formelastomeric products. The methyl group in a silicone may be substitutedby a variety of other substituents including for example, phenyl, vinyl,and hydrogen. Conventional silicones are the trimethylsiloxy terminatedpolydimethylsiloxanes. Such materials are available in viscositiesranging from 0.65 to 2,500,000 centistokes. Substituents on the siliconconsist of methyl groups or oxygen. Termination of the polymer chainprevents viscosity change and other alterations of the physicalproperties of the silicone polymeric materials. Thepolydimethylsiloxanes exhibit characteristic properties of low viscositychange with temperature; thermal stability; oxidative stability;chemical inertness; non-flammability; low surface tension; highcompressibility; shear stability; and dielectric stability. In resinforming polysiloxanes, some of the methyl groups are hydrolyzable andpermit the formation of Si-O-Si cross-links upon heating in the presenceof a catalyst, but in the organosilicon fluids and oils, substantiallyall of the methyl groups are non-hydrolyzable and the fluid is heatstable.

The polydimethylsiloxane fluid used herein as the antifoam agent is ahigh molecular weight polymer having a molecular weight in the rangefrom about 200 to about 200,000, and has a viscosity in the range fromabout 20 to 2,000,000 centistokes, preferably from about 500 to 50,000centistokes, more preferably about 550 to 1,200 centistokes at 25° C.The siloxane polymer is generally end-blocked either with trimethylsilylor hydroxyl groups but other end-blocking groups are also suitable. Thepolymer can be prepared by various techniques such as the hydrolysis andsubsequent condensation of dimethyldihalosilanes, or by the cracking andsubsequent condensation of dimethylcyclosiloxanes.

The polydimethylsiloxane fluid antifoam agent can be present incombination with particulate silica. Such combinations of silicone andsilica can be prepared by affixing the silicone to the surface ofsilica, for example, by means of the catalytic reaction disclosed inU.S. Pat. No. 3,235,509. Foam regulating agents comprising mixtures ofsilicone and silica Prepared in this manner preferably comprise siliconeand silica in a silicone:silica ratio of from 20:1 to 200:1, preferablyabout 25:1 to about 100:1. The silica can be chemically and/orphysically bound to the silicone in an amount which is preferably about0.5% to 5% by weight, based on the silicone. The particle size of thesilica employed in such silica/silicone foam regulating agents is finelydivided and should preferably be not more than 100 microns, preferablyfrom 2 microns to 20 microns.

Alternatively, silicone and silica can be prepared for use in theantifoam agent by admixing a silicone fluid of the type herein disclosedwith a hydrophobic silica having a particle size and surface area in therange disclosed above. Any of several known methods may be used formaking a hydrophobic silica which can be employed herein in combinationwith a silicone as the foam regulating agent. For example, a fumedsilica can be reacted with a trialkyl chlorosilane (i.e., "silanated")to affix hydrophobic trialkylsilane groups on the surface of the silica.In a preferred and well known process, fumed silica is contacted withtrimethylchlorosilane. A preferred material comprises a hydrophobicsilanated, most preferably trimethylsilanated, silica, intimatelyadmixed with a dimethyl silicone fluid having a molecular weight in therange of from about 200 to about 200,000, at a weight ratio of siliconeto silanated silica of from about 20:1 to about 200:1, preferably fromabout 20:1 to about 100:1.

Yet another type of material suitable herein as the polydimethylsiloxanefluid antifoam comprises polydimethylsiloxane fluid, a silicone resinand silica. The silicone "resins" used in such compositions can be anyalkylated silicone resins, but are usually those prepared frommethylsilanes. Silicone resins are commonly described as"three-dimensional" polymers arising from the hydrolysis of alkyltrichlorosilanes, whereas the silicone fluids are "two-dimensional"polymers prepared from the hydrolysis of dichlorosilanes. The silicacomponents of such compositions are microporous materials such as fumedsilica aerogels and xerogels having particle sizes and surface areasherein-above disclosed.

The mixed polydimethylsiloxane fluid/silicone resin/silica materialsuseful in the present compositions as antifoam agent can be prepared inthe manner disclosed in U.S. Pat. No. 3,455,839. Preferred materials ofthis type comprise:

(a) from about 10 parts to about 100 parts by weight of apolydimethylsiloxane fluid having a viscosity in the range from 20 to30,000 mm/s at 25° C.:

(b) 5 to 50 parts by weight of a siloxane resin composed of (CH₃)₃SiO_(1/2) units and SiO₂ units in which the ratio of the (CH₃)₃SiO_(1/2) units to the SiO₂ units is within the range of from 0.6/1 to1.2/1: and

(c) 0.5 to 5 parts by weight of a silica aerogel, precipitated silica,or hydrophobic silica. Such mixtures can also be sorbed onto and into awater-soluble solid.

Essentially, the antifoam of the present invention includes silicaparticles, one of an oil of mineral oil, vegetable oil, and siliconeoil, encapsulated in a water soluble solid such as sugar or a hydrolysisproduct of starch. The encapsulated antifoam has been found to inhibitfoaming in aqueous yeast broths of Saccharomyces cerevisiae. and at thesame time, the encapsulated antifoams of the present invention do notcause severe irreversible fouling of the membranes akin to the antifoamformulations of the prior art. Several examples, testing procedures, andtables, are shown hereinafter in order to more completely illustrate theconcepts of the present invention. Percentages of materials expressed inthe examples, tests, and tables, are intended as weight percentages,unless otherwise specified.

The antifoam can be delivered in a dry solid capsule or powder form anddissolved to release the antifoam. The encapsulation is achieved bydispersing the oil and silica into a heated sugar and water solution.The sugar melt is cooled and solidified entrapping the defoaming activemoiety. The solid is broken into various particle sizes. Alternatively,the melt can be dried and formed into microparticles by spray drying.The antifoam can be used in fermentation broths to inhibit foamingwithout causing fouling of the ultrafilters used in enzyme concentrationdownstream of the bioreactor. Contact with an aqueous solution causesdissolution of the sugar encapsulator releasing the antifoam.

EXAMPLE I

A solution of 30-35% maltodextrin and 30-35% water was heated withstirring until the maltodextrin melted and dissolved in water. Asolution of 3-10% vegetable oil and hydrophobic silica was added. Themixture was heated and stirred until the oil and silica were dispersed.The mixture was poured onto a silicon-treated paper and allowed to dryovernight. The hardened crystalline material was broken into variousparticle sizes.

EXAMPLE II

A solution of 30-35% maltodextrin and 30-35% water was heated withstirring until the maltodextrin melted and dissolved in water. Asolution of 3-10% mineral oil and hydrophobic silica was added. Themixture was heated and stirred until the oil and silica were dispersed.The water was removed via spray drying, and the powder and granules werecollected.

Table I shows compositions A-D prepared in accordance with Examples Iand II.

                  TABLE I                                                         ______________________________________                                                   A     B         C       D                                          ______________________________________                                        Maltodextrin*                                                                              63.63%  60.00%    60.00%                                                                              65.57%                                   Water        30.91%  35.00%    5.60% 30.16%                                   Soybean oil   4.55%  --        --    --                                       Mineral oil  --       4.00%    4.00%  3.94%                                   Hydrophobic silica                                                                          .91%    1.00%    0.40%  0.33%                                   ______________________________________                                         *=Manufactured by A. E. Staley Mfg. Co., Decatur, Illinois, and sold unde     the Trademark STARDRI ®.                                             

The defoaming efficiency of compositions A-D prepared above in ExamplesI and II, and shown in Table I, was determined by using a one thousandmilliliter graduated cylinder, equipped with a gas dispersion tubeterminating in a stone sparger. Two hundred milliliter samples wereloaded into the cylinder and an air flow rate of five hundredmilliliters per minute was used to sparge the contents. The contentswere sparged with air continuously while at the same time measuring thefoam height at each fifteen second interval. The control sample includedtwo hundred milliliters of deionized water containing three percent byweight of S. cerevisiae, but containing no antifoam agent. The yeast S.cerevisiae was added to simulate a fermentation broth. Test samplesincluding twenty-five parts per million of each of antifoam compositionsA-D, were prepared in two hundred milliliters of deionized watercontaining three percent by weight of S. cerevisiae, and sparged asindicated above. The results of such tests of the defoaming ability ofthe encapsulated antifoams of the present invention can be seen in TableII.

                  TABLE II                                                        ______________________________________                                                    Foam Height (ml.)                                                 Time(sec.)                                                                             Control  X*        A     B    C    D                                 ______________________________________                                        15       500      400       400   300  340  450                               30       670      500       440   330  320  450                               45       760      650       400   350  310  470                               60       770      650       350   350  310  400                               75       750      800       350   350  300  350                               300      --       >1000     300   350  300  300                               ______________________________________                                         *=Polygloycol based antifoam for comparison.                             

In Examples III and IV set forth below, additional encapsulatedantifoams were prepared including silicone based oils. Compositions E-Gprepared in accordance with Examples III and IV are shown in Table III.In Table III, compound Y is a polydimethylsiloxane fluid having aviscosity of about 550 centipoises measured at twenty-five degreesCentigrade, and including a silica filler. Compound Z is also a silicafilled polydimethylsiloxane fluid but of a viscosity of about 1200centipoises. The defoaming efficiency of these encapsulated siliconeantifoam formulations E-G was tested in accordance with the procedureoutlined hereinbefore, and the results of such defoaming tests is shownin Table IV.

EXAMPLE III

A solution of 55-95% maltodextrin, 5-30% silicone antifoam compound and1-35% water was heated with stirring until the maltodextrin melted anddissolved in water. The solution was poured onto silicon-treated paperand allowed to dry overnight. The hardened crystalline material wasbroken into various particle sizes.

EXAMPLE IV

A solution of 55-95% maltodextrin and 30-35% water was heated withstirring until the maltodextrin melted and dissolved in water siliconeantifoam compound, 3-10% by weight, was added. The mixture was heatedand stirred until the compound was dispersed. The water was removed viaspray drying, and the powder and granules were collected.

                  TABLE III                                                       ______________________________________                                                  E          F       G                                                ______________________________________                                        Maltodextrin*                                                                             60.0%        --      57.14%                                       Maltodextrin**                                                                            --           62.5%   --                                           Compound Y   5.0%        20.83%  --                                           Compound Z  --           --      14.29%                                       Water       35.0%        16.67%  28.57%                                       ______________________________________                                         *=See Table I.                                                                **=Sold under the Trademark MALTRIN ®.                               

                  TABLE IV                                                        ______________________________________                                                       Foam Height (ml.)                                              Time(sec.)  Control  E          F    G                                        ______________________________________                                        15          500      300        450  325                                      30          670      300        550  400                                      45          760      350        600  450                                      60          770      350        600  450                                      75          750      240        600  450                                      ______________________________________                                    

It has been found in accordance with the teaching of the presentinvention, that any membrane fouling which may occur, is reversible, andthat the ultrafiltration membrane surface can be cleaned. Such cleaningmay be accomplished by passing through the membrane about ten liters of0.1M sodium hydroxide solution, or about ten liters of 0.5 weightpercent of TERGAZYME® enzymatic cleaner, for fifteen minutes. Two tenliter volumes of clear deionized water are flushed through the systemfollowing this treatment.

While particular weight percentages of ingredients of the encapsulatedantifoams are set forth in Examples I-IV, the compositions of thepresent invention are not limited to such amounts, and the variousingredients may be employed in other and varying percentages. Forexample, maltodextrin may be present and can constitute from about 55-95weight percent of the encapsulated antifoam formulation. The silicafiller can be present and may constitute from about one to about nineweight percent. The siloxane fluid is preferably employed in the amountof from about three to about twenty weight percent; while vegetable oilsand mineral oils can comprise from about five to about thirty percent byweight.

In the following table, data are set forth indicating results obtainedfrom tests conducted for the purpose of determining fouling and cloggingwhich may occur as a result of the presence of several antifoamformulations in a solution of deionized water containing about onehundred parts per million of antifoam formulation. A membraneconstructed of a polysulfone material in sheet form and having anapproximate molecular weight cut off of about 25,000 was employed. Thetable expresses the percent relative flux obtained during such tests asa function of the time in minutes which elapsed, in order for fiftymilliliters of filtrate to be collected through the membrane. The fluxfollowing cleaning of the membrane, is also reflected in Table V. Asnoted previously, flux is an expression of filtration rate, and the mostideal flux is related to the value obtained when pure water, free ofantifoam agent, is passed through the membrane. Solutions containingencapsulated antifoam formulations prepared in accordance with thepresent invention, as well as comparitive antifoam formulations, areshown in Table V.

                  TABLE V                                                         ______________________________________                                        % RELATIVE FLUX*                                                              Filtration Control                                                            Time(min.) (Water)  A         X***  F                                         ______________________________________                                         0         100      100       100   100                                       30         91.0     87.6      23.7  80.4                                      60         91.0     87.6      23.7  74.3                                      90         88.8     87.6      23.7  75.4                                      120        82.1     82.3      23.2  69.0                                      Flux after --       --        73.1  87.5                                      cleaning**                                                                    ______________________________________                                         *The initial permeate flux of deionized water was measured and considered     100%. The permeate flux was measured at 30 minute intervals after additio     of antifoam and compared to the initial flux.                                 **The membranes were treated with TERGAZYME ®, an enzymatic cleaner,      for ten minutes, rinsed with deionized water and the permeate flux            remeasured.                                                                   ***Polyglycol based antifoam for comparison.                             

It will be apparent from the foregoing that many other variations andmodifications may be made in the structures, compounds, compositions,and methods described herein without departing substantially from theessential features and concepts of the present invention. Accordingly,it should be clearly understood that the forms of the inventiondescribed herein are exemplary only and are not intended as limitationson the scope of the present invention.

That which is claimed is:
 1. In a method for processing aqueousfermentation broths in a bioreactor vessel, in which a foam inhibitor isadded to the fermentation broth in the bioreactor vessel in order toprevent the accumulation and buildup of foam in the bioreactor vesselcaused by oxygen sparging of the fermentation broth contained therein,and in which the aqueous fermentation broth processed in the bioreactorvessel is conveyed as a feed solution to an ultrafiltration systemincluding a membrane for concentrating the aqueous fermentation broth,the ultrafiltration system being located downstream of the bioreactorvessel, the improvement comprising reducing the amount of fouling of themembrane in the ultrafiltration system by adding to the aqueousfermentation broth in the bioreactor vessel as the foam inhibitor, anantifoam which is an oil based liquid in the form of droplets, thedroplets of the oil based liquid antifoam being dispersed, encased,entrapped, and imbedded, within solid particles of a water solubleencapsulating material.
 2. The method of claim 1 wherein the oil basedliquid antifoam is selected from the group consisting of silicone oils,vegetable oils, and mineral oils.
 3. The method of claim 2 wherein thewater soluble encapsulating material is selected from the groupconsisting of sugars and hydrolysis products of starch.
 4. The method ofclaim 3 wherein the water soluble encapsulating material ismaltodextrin.
 5. The method of claim 2 wherein the water solubleencapsulating material is selected from the group consisting ofmaltodextrin, glucose, maltose, sucrose, fructose, xylose, and lactose.6. The method of claim 1 wherein the antifoam is free of surfactants,thickeners, and coagulants, which tend to clog the membrane.